Acetonitrile → 3-[1-(2-Chlorophenyl)-ethoxy]-5-cyanoacetyl-thiophene-2-carboxylic acid methyl ester

HRID 1930795Notes

Reaction equation

HRID 1930795 reaction equation
[CH3:1][C:2]#[N:3].[H-].[Na+].[CH3:6][O:7][C:8]([C:10]1[S:11][C:12]([C:25](OC)=[O:26])=[CH:13][C:14]=1[O:15][CH:16]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[Cl:24])[CH3:17])=[O:9]>O1CCOCC1>[CH3:6][O:7][C:8]([C:10]1[S:11][C:12]([C:25](=[O:26])[CH2:1][C:2]#[N:3])=[CH:13][C:14]=1[O:15][CH:16]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[Cl:24])[CH3:17])=[O:9]

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 24758Sodium hydrideHCID 57965599HCID 57965599, compound

Product 1

HCID 667303243-[1-(2-Chlorophenyl)-ethoxy]-5-cyanoacetyl-thiophene-2-carboxylic acid methyl esterYield 6%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

MeCN (231 mg, 5.62 mmol, 1.0 Eq.) was added to a suspension of NaH (225 mg, 60% dispersion in mineral oil, 5.62 mmol, 1.0 Eq.) in anhydrous dioxane (30 mL) at ambient temperature under nitrogen. After stirring for 25 minutes 3-[1-(2-Chlorophenyl)-ethoxy]-thiophene-2,5-dicarboxylic acid dimethyl ester (1.94 g, 5.62 mmol, 1.0 Eq.) was added and the reaction heated at reflux overnight. The reaction was cooled to ambient temperature, quenched with water and partitioned between EtOAc (100 mL) and brine (100 mL). The aqueous phase was extracted with EtOAc (2×50 mL) and the combined organic extracts dried (MgSO4) and concentrated in vacuo. The crude product was purified by column chromatography (50% EtOAc/Petroleum ether) to give the sub-title compound as a white solid (115 mg, 0.32 mmol, 6%); 1H NMR (400 MHz, d-6 DMSO) δ 1.61 (3H, d), 3.82 (3H, s), 4.62-4.74 (2H, m). 5.88 (1H, q), 7.35 (1H, t), 7.40 (1H, t), 7.48 (1H, d), 7.73 (1H, d), 7.91 (1H, s).

Workup

  1. additionwas added
  2. temperaturethe reaction heated
  3. temperatureat reflux overnight
  4. customquenched with water
  5. custompartitioned between EtOAc (100 mL) and brine (100 mL)
  6. extractionThe aqueous phase was extracted with EtOAc (2×50 mL)
  7. dry with materialthe combined organic extracts dried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by column chromatography (50% EtOAc/Petroleum ether)

Sources & evidence

ORD record
ord-2976627e6b3d4872995afe1c787713e6
Source dataset
uspto-grants-2012_05
Patent number
US08188134B2

Reaction notes

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